1. Field of the Invention
The present invention relates to new peptides and polypeptides that are powerful inhibitors of tartar (dental calculus) formation.
2. Discussion of Background
Biological mineralization is a fundamental process in nature. Formation of bones and teeth from calcium phosphate and formation of shells and reefs from calcium carbonate are but two examples of this process.
Unfortunately, mineral deposits also frequently occur where they are not wanted. In the body, mineral deposition may contribute to dental plaque, hardening of the arteries, various organ stones, and failure of prosthetic devices like implanted heart valves. In the marine environment, the biomineral structures may cause problems as in the case of barnacles growing on the hulls of ships, adding extra bulk and creating drag. In industry, mineral scale forms on surfaces of cooling towers and other devices preventing their proper operation as heat exchangers and frequently promoting localized corrosion.
Because of the problems associated with unwanted mineral deposition, much effort has been devoted to finding mineralization inhibitors, particularly in industry, that might be used to prevent harmful mineral formation.
Molecules for prevention of mineral deposition have ranged from simple ions like Mg.sup.+2 (Pytkowicz, R. M., J. Geol. 73, 196-199 (1965)) and PO.sub.4.sup.3- or pyrophosphate (Simkiss, K., Biol. Rev. 39, 487-505 (1964)) to more complex organic materials. Inhibition by simple ions is based on the ability of these ions to interfere with the orderly formation of the crystalline lattice of the mineral, such as CaCO.sub.3. In addition, phosphate and polyphosphates have the property of protecting metallic surfaces by forming very thin films that cover potential sites of corrosion on the surfaces.
Phosphonates were introduced in the late 1960's (Ralston, U.S. Pat. No. 3,336,221 (1967)). These are small organic molecules with PO.sup.3 groups attached directly to a central carbon atom via a covalent bond to phosphorus. The phosphonates are very effective inhibitors of crystallization that work by adsorbing to crystal surfaces. Hydroxyethylidene diphosphonate (HEDP) is perhaps the most widely used phosphonate, still among the most powerful inhibitors of CaCO.sub.3 formation known.
Use of phosphonates has some disadvantages though. For example, phosphonates can be degraded during chlorination which in turn may lead to elevated phosphates and associated phosphate scales. Phosphonates themselves may also precipitate under common operating conditions. HEDP is an exceptionally effective inhibitor of crystal nucleation on a weight basis as shown by its effect on lengthening the induction period prior to crystal growth, but it is not at all effective at inhibiting crystal growth after it begins, (Sikes and Wheeler, CHEMTECH, in press (1987)).
More recently, as a result of continuing efforts to identify better inhibitors, polyacrylate and other polyanionic materials have been identified (Rohm and Haas Company, Technical Bulletin CS-513A (1985), Fong and Kowalski, U.S. Pat. No. 4,546,156 (1985)). In the 1980's, antiscaling and anticorrosion technology has been based increasingly on use of synthetic polymers under alkaline conditions. The current trend in synthetic polymers for water treatment is the use of random copolymers or terpolymers with alternating side groups of COO- with groups like OH, CH.sub.3, PO.sub.3.sup.2-, SO.sub.3.sup.2- etc.
A new approach to identifying mineralization inhibitors was disclosed by Sikes and Wheeler U.S. Pat. Nos. 4,534,881 (1985); 4,585,560 (1986); and 4,603,006 (1986) and Wheeler and Sikes, U.S. Pat. No. 4,587,021 (1986). In these patents, it was disclosed that proteins and polysaccharides extracted from biological minerals like oyster shells are strong inhibitors of crystallization. By studying the structure of the natural molecules, particularly the proteins, clues to the chemical nature required for activity of synthetic polyamino acids were obtained. Based on this, certain polyanionic polyamino acids including random copolymers of negatively charged residues and nonionic residues were identified as useful inhibitors.
Some other patents related to this invention are the following:
Gaffar, U.S. Pat. No. 4,339,431, discloses copolymers of glutamic acid and alanine which are used as anticalculus agents in dentifrices or mouthwashes. The copolymers disclosed therein are random copolymers.
Segrest et al, U.S. Pat. No. 4,643,988, discloses polypeptides having a non-clustered arrangement of anionic and hydrophic amino acids, which were used for treatment of atherosclerosis (perhaps by preventing deposition of certain minerals).
Buck, U.S. Pat. No. 4,362,713, is directed to compositions and methods for preventing attachment of dental plaque to the surface of teeth by the use of salts of certain maleic acid copolymers.
In spite of the above approaches to solving the problems of unwanted mineral deposition, there remains a strong need for a new and more powerful inhibitors of mineral deposition which could be used in the body, in a marine environment, or industrially.